PurposeAmphotericin B (AMB) is one of the major antifungal drugs used in the management of aspergillosis and is especially recommended for treating triazole-resistant strains of Aspergillus fumigatus. However, relatively little is known about the AMB susceptibility patterns of A. fumigatus in many parts of the world. This study aims to describe the AMB susceptibility patterns in Hamilton, Ontario, Canada.MethodsThe in vitro susceptibilities of 195 environmental and clinical A. fumigatus isolates to AMB were tested by the broth microdilution method as per the Clinical and Laboratory Standards Institute’s guidelines. Catalase-generated oxygen bubbles trapped by Triton X-100 were used to quantify catalase activity in a representative group of isolates.ResultsOf the 195 isolates, 188 (96.4%) had the minimum inhibitory concentration (MIC) of AMB ≥2 mg/L, with approximately 80% and 20% of all clinical and environmental isolates having MICs of ≥ 4 mg/L. Overall, the clinical isolates were less susceptible to AMB than environmental isolates (P-value <0.001). The strain with the highest AMB MIC (16 mg/L) had one of the highest catalase activities. However, there was no correlation between AMB MIC and catalase activity in our sample.ConclusionThe widespread AMB resistance suggests that using AMB in the management of A. fumigatus infections in Hamilton would likely result in treatment failure. Although high catalase activity may have contributed to AMB resistance in some isolates, the mechanism(s) for the observed AMB resistance in Hamilton is unknown and likely complex.
Summary Background The sister yeast species Cryptococcus neoformans (serotype A) and Cryptococcus deneoformans (serotype D) are causative agents of deadly cryptococcosis and fungal meningoencephalitis. These haploid yeasts can hybridise in nature, giving rise to AD hybrids that are predominantly diploid or aneuploid. Despite their increasing prevalence in clinical settings, much remains unknown about the allelic distribution patterns in AD hybrid strains. Objectives This study aims to characterise allele distributions in AD hybrids derived from the same basidium as well as from multiple basidia in a laboratory‐derived C neoformans × C deneoformans hybrid cross. Methods We dissected a total of 1625 basidiospores from 31 basidia. The 297 basidiospores that successfully germinated were genotyped by molecular characterisation of 33 markers using PCR‐RFLP, with at least two markers on each of the 14 chromosomes in the genome. Results Of the 297 strains, 294 contained at least one heterozygous locus, with a mean heterozygosity of ~30% per strain. Most hybrid genomes and chromosomes displayed significantly distorted allele distributions, with offspring originating from the same basidium tended to have alleles at different loci from the same parent. More basidia were skewed in favour of C deneoformans alleles, the mitochondria‐donor parent, than the C neoformans alleles. Conclusions The divergence between C neoformans and C deneoformans genomes has likely created co‐adapted allelic combinations, with their co‐segregation in hybrid offspring imparting a significant fitness benefit. However, the diversity of genotypes recovered here in a single hybridisation event indicates the enormous capacity of AD hybrids for adaptation and diversification.
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